A Bioactive Chemical Markers Based Strategy for Quality Assessment of Botanical Drugs: Xuesaitong Injection as a Case Study

Abstract

Current chemical markers based quality assessment methods largely fail to reflect intrinsic chemical complexity and multiple mechanisms of action of botanical drugs (BD). The development of novel quality markers is greatly needed. Here we propose bioactive chemical markers (BCM), defined as a group of chemo-markers that exhibit similar pharmacological activities comparable to the whole BD, which can therefore be used to effectively assess the quality of BD. As a proof-of-concept, a BCM-based strategy was developed and applied to Xuesaitong Injection (XST) for assessing the efficacy and consistency of different batches. Firstly, systemic characterization of chemical profile of XST revealed a total number of 97 compounds. Secondly, notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd were identified as BCM of XST on treating cardiovascular and cerebrovascular diseases according to Adjusted Efficacy Score following an in vivo validation. Analytical method for quantification of BCM was then developed to ensure the efficacy of XST. Finally, chemical fingerprinting was developed and used to evaluate the batch-to-batch consistency. Our present case study on XST demonstrates that BCM-based strategy offers a rational approach for quality assessment of BD and provides a workflow for chemistry, manufacturing, and controls (CMC) study of BD required by regulatory authority.

Developing Robust Standardised Analytical Procedures for Cannabinoid Quantification: Laying the Foundations for an Emerging Cannabis-Based Pharmaceutical Industry

“…Reports of inaccurate labelling and batch-to-batch variation of active ingredients within magistral CME preparations confirm fears that these products lack standardisation [29, 91, 92]. Being able to characterise accurately the complexity of botanical drug forms and to discriminate the efficacy of their constituents both singularly and in combination remains challenging [93]. This is highlighted by the fact that, so far, only two botanical drug forms have met the Botanical Guidance definition of a botanical drug product and received New Drug Application approval and prescription drug marketing authorisation by the FDA (Veregen® from Camellia sinensis as well as Fulyzaq TM [Mytesi TM ] from Croton lechleri ) [30].…”

Recent Development of Quality Control Methods for Herbal Derived Drug Preparations

“…EMC or EEC was determined using an (animal) bioactivities model. Lee et al [73] determined 14 markers simultaneously (Herb MaRS ranked >3) from Chinese medicine formulations containing a seven herbs mixture; the same concept using many markers as a QC tool was developed by Yang et al (74); these markers were named bioactive chemical markers (BMC). According to the description of EMC, EEC and BMC, these categories of marker could also be defined as QA-marker(s).…”

<p>Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases</p>

“…NG-R1 has been identified as one of the bioactive chemical markers of Xuesaitong Injection (XST), 94 which is made of the saponins from P. notoginseng and has been extensively employed in clinic for managing cardiovascular and cerebrovascular diseases in China. 95 Naodesheng (NDS) is the TCM prescription widely used for clinic management of cerebral infarction in China. NG-R1 is one of the bioactive compounds in NDS, which has been demonstrated to improve neurobehavioral activity, decrease the cerebral infarct area, and attenuate pathological features in middle cerebral artery occlusion (MCAO) rat models.…”